Our laboratory has discovered that the subfornical organ is a brain substrate mediating drinking. In particular it is highly responsive to direct application of cholinergic agents, carbachol acetylcholine and even more sensitive to the octapeptide, angiotensin-II. The latter agent may be particularly important in the coordinated body fluid regulation of both central nervous system structures (i.e., subfornical organ) and peripheral organs (i.e., the kidney). For this reason the present proposal focuses on angiotensin-II actions on the subfornical organ. Attention is first directed at the exclusivity of the subfornical organ among circumventricular structures in mediating angiontensin-II induced drinking. Experiments are then described which will enable the determination of the output pathways from the subfornical organ using both intracranial and intravenous infusion of angiotensin-II. Third, the influence of angiotensin-II on cholinergic induced drinking will be studied. Finally, in our ongoing program to relate subfornical organ function to physiological function, a study is proposed to determine the role of this structure in the heightened water intake seen during exercise. Because of the role of angiotensin-II in mediating high blood pressure and heart attacks, knowledge of the brain sites of action of this drug are important particularly as they directly affect these clinical states and the therapeutic approaches to their solution. BIBLIOGRAPHIC REFERENCES: Simpson, J. B. and Routtenberg, Al., Subfornical organ lesions reduce intravenous angiotensin-induced drinking. Brain Research, 88 (1975) 154-161.